Circ_0000467 Exerts an Oncogenic Role in Colorectal Cancer via miR-330-5p-Dependent Regulation of TYRO3.

Abstract

Colorectal cancer (CRC) remains one of the most frequent neoplasms of digestive tract worldwide. Circular RNAs (circRNAs) have been identified to serve crucial regulatory roles in the pathogenesis of human cancers. However, the role and regulatory mechanism of circ_0000467 in the progression of CRC are still unclear. The expression levels of circ_0000467, microRNA-330-5p (miR-330-5p), and tyrosine receptor kinase 3 (TYRO3) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-330-5p and circ_0000467 or TYRO3 was validated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenograft tumor assay and Immunohistochemistry (IHC) assay were implemented to analyze CRC tumor growth in vivo. Circ_0000467 was a stable circRNA and was highly expressed in CRC tumor tissues and cells. Silencing of circ_0000467 could inhibit the proliferation, migration, invasion, and glycolysis and accelerated the apoptosis of CRC cells in vitro and hindered tumor growth in vivo. Mechanistically, circ_0000467 directly interacted with miR-330-5p and circ_0000467 depletion inhibited CRC cell malignant progression by regulating miR-330-5p. Furthermore, TYRO3 was a target of miR-330-5p and circ_0000467 upregulated TYRO3 expression by sponging miR-330-5p. Moreover, TYRO3 overexpression counteracted the inhibitory effect of miR-330-5p overexpression or circ_0000467 knockdown on CRC cell progression. Altogether, circ_0000467 knockdown suppressed CRC cell malignant development through modulating the miR-330-5p/TYRO3 network, providing a novel molecular target of CRC therapy.